[Malignant mesothelioma: analysis of a hospital case series]. / Mesotelioma maligno: analisi di una casistica ospedaliera.

The 2000-2010 case record of our Institute includes 77 cases of malignant mesothelioma (MM) [67 pleural (40 males, 27 females; mean age 63.9 years), 9 peritoneal (7 males, 2 females; 67.9 years) and one testicular (38 year-old man)], often associated, with various degree of probability, to previous asbestos exposure (occupational or environmental). Twenty-four patients with pleural MM had undergone surgery (12 pleural decortication and 12 pneumonectomy), with median survival, respectively, of 14 +/- 4.33 (standard error) and 38 +/- 4.27 months, longer than that recorded without surgery (8 +/- 0.94 months). Four peritoneal cases underwent peritonectomy with hyperthermic intraoperative chemotherapy: one is still alive 20 months after diagnosis, the others died at 8, 18 and 36 months. The testicular case is still living 6 years after radical orchidectomy. In conclusion, due to past asbestos use, MM is often observed in the current clinical practice. Patients treated surgically present longer survivals.

Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.

BACKGROUND: Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma. OBJECTIVES: It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea. METHODS: Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m(3) for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained. RESULTS: In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 +/- 12.1% (p < 0.01). The cholinergic nerve-mediated contractions to electrical field stimulation and the muscular response to histamine were not modified by ammonium persulphate exposure. The muscular response to carbachol was unaffected up to 1 microM. Conversely, the response to the maximal concentration of carbachol (3 microM) was increased (p < 0.01). CONCLUSION: Ammonium persulphate inhalation at high concentrations impairs the nervous NANC inhibitory control in the guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma.

Two cases of asbestosis and one case of rounded atelectasis due to non-occupational asbestos exposure.

Asbestos is a well-known cause of several neoplastic (malignant mesothelioma, lung cancer) and non-neoplastic (asbestosis, pleuropathies) occupational diseases. Lower-level exposure in the general environment may induce pleural plaques and thickenings, and is associated with an increased mesothelioma risk. We present two patients (a 68-year-old man and a 72-year-old woman) who developed asbestosis (in association with pleural plaques and calcifications), and a 78-year-old man who developed rounded atelectasis (with pleural plaques and benign effusion), after living for several decades in the proximity of large Italian asbestos-cement plant. None of them had been exposed to asbestos occupationally. Besides living in a contaminated area, the woman used to clean the work clothes of her brother, who was employed in the local asbestos factory. The three cases indicate that non-neoplastic, long-latency asbestos-related diseases which are usually observed as a consequence of occupational exposures, may rarely develop in subjects living in contaminated geographical sites and buildings. These unusual environmental diseases raise the diagnostic problem of differentiating them from other, more common respiratory illnesses, and impose the duties of patient notification, assessment and follow-up, to assess the possibility of progression of disease and increased neoplastic risk.

[Neurally-mediated syncope and occupational accidents: prevention strategies and case report]. / Sincope neuromediata e infortuni sul lavoro: strategie preventive e considerazioni su un caso clinico.

A bus driver came to our observation after an occupational traffic accident due to a syncopal event. The positive result of the tilt testing demonstrated the neurally-mediated nature of the syncope. The accident involved approximately 40 people (all the bus passengers), fortunately without severe injuries or deaths. The described episode indicates the need for a procedural algorithm, commonly approved, applicable in the field of prevention, for those occupational categories with severe accident risk. Indeed, the possibility exists to identify at least a part of the subjects predisposed to neurally-mediated syncope. Fundamental steps for such screening are history taking (looking for previous events, familiarity), the physical examination (useful, for example, to exclude orthostatic hypotension or carotid sinus syncope), and, in particular, the tilt testing, a diagnostic investigation recommended for all the workers who have had a previous syncope and are at high occupational accident risk. Moreover, the reported case recalls the need to strengthen the collaboration between the cardiologist and the occupational health physician.

Role of carbon monoxide in electrically induced non-adrenergic, non-cholinergic relaxations in the guinea-pig isolated whole trachea.

BACKGROUND AND PURPOSE: Nitric oxide (NO) and vasoactive intestinal peptide (VIP) are considered transmitters of non-adrenergic, non-cholinergic (NANC) relaxations in guinea-pig trachea, whereas the role of carbon monoxide (CO) is unknown. This study was designed to assess the participation of CO, and to investigate the localization of haem oxygenase-2 (HO-2), the CO-producing enzyme, in tracheal neurons. EXPERIMENTAL APPROACH: NANC responses to electrical field stimulation (EFS) at 3 and 10 Hz were evaluated in epithelium-free whole tracheal segments as intraluminal pressure changes. Drugs used were: L-nitroarginine methyl ester (L-NAME, 100 microM) to inhibit NO synthase (NOS), alpha-chymotrypsin (2 U ml(-1)) to inactivate VIP, zinc protoporphyrin-IX (ZnPP-IX, 10 microM) to inhibit HO-2, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM), a soluble guanylyl cyclase inhibitor. For immunohistochemistry, tissues were exposed to antibodies to PGP 9.5, a general neuronal marker, HO-2 and NOS, and processed with an indirect immunofluorescence method. KEY RESULTS: alpha-Chymotrypsin did not affect NANC relaxations. ODQ inhibited NANC responses by about 60%, a value similar to that obtained by combining L-NAME and ZnPP-IX. The combination of ODQ, L-NAME and ZnPP-IX reduced the responses by 90%. Subpopulations of HO-2 positive neurons containing NOS were detected in tracheal sections. CONCLUSIONS AND IMPLICATIONS: In the guinea-pig trachea, NANC inhibitory responses at 3 and 10 Hz use NO and CO as main transmitters. Their participation is revealed following inhibition of NOS, HO-2 and soluble guanylyl cyclase. The involvement of CO as a relaxing transmitter paves the way for novel therapeutic approaches in the treatment of airway obstruction.

[Rhabdomyolysis in a worker exposed to paraffinic mineral oils. Unusual association with bronchiolitis obliterans and organizing pneumonia (BOOP)]. / Rabdomiolisi in operaio esposto ad olii minerali paraffinici. Insolita associazione con bronchiolite obliterante e polmonite organizzativa (BOOP).

We describe a 29-year-old worker; exposed to metal dust, sawdust and paraffinic mineral oils in a factory producing accessories for leather articles and clothing, who came to observation with fever (39 degrees C), chest pain and marked increase of muscular enzymes. Chest computed tomography showed two areas of lung consolidation, that subsequently appeared enlarged with central escavation. Lung biopsy lead to the diagnosis of BOOP. The case has been reported to the judicial and workers' compensation authorities as probable occupational toxic myopathy. Indeed, exposure to paraffinic mineral oils is a known, though unusual, cause of rhabdomyolysis. The association with BOOP has never been previously described.

[Management of occupational stress among patients with cardiac diseases]. / Gestione dello stress occupazionale in pazienti cardiopatici.

The object of our study was the evaluation of psycophysic condition, stress perception and coping in a sample of subject in cardiac rehabilitation. Our study recruited 48 worker patients (44 male, M = 50.5 +/- 8.8; 4 female, M = 50.8 +/- 8.7). They were submitted to: 1) cardiac evaluation and rehabilitation in DH regimen; 2) psychological assessment; 3) work's characteristic evaluation. The evaluation were made at the moment of recruitment and six month later 42 subjects went back to work after 81.8 +/- 49 days; 2 subjects had a worsening of their clinic conditions not consistent with an occupational resumption; 4 subjects didn't go back to work. In the 42 worker subjects we have find a significant decrease of anxiety (p < 0.019) and depression levels (p < 0.004); a significant improvement of Quality of Life perception in its physical (p < 0.000) and psychic aspects (p < 0.021) and an improvement about the ability to reorganize the work to better ménage stress (p < 0.012).

[A case of pleural mesothelioma caused by unusual occupational exposure to asbestos in the wool industry]. / Un caso di mesotelioma pleurico da inusuale esposizione professionale ad amianto nell'industria della lana.

We report the case of a 73-year-old worker who died of pleural mesothelioma, after being employed for 35 years in a wool textile plant of Biella (Italy). Close investigations revealed that he provided for the maintenance of materials and machines. In particular, he used to replace asbestos parts such as rings, joints and insulations of pipelines (dyeing unit), as well as brake linings of warping, looming and combing machines. Beside confirming the importance of an accurate occupational anamnesis to recognize work-induced cancers, the case draws the attention on the risk of mesothelioma in the wool industry, an occupational setting that is not usually considered as a potential source of exposure to asbestos fibres. Such pollution might explain the increased mortality due to pleural mesothelioma in the Biella area (characterized by a prosperous textile industry), reported in previous epidemiological studies.

[Small cell carcinoma of the prostate. Description of a case]. / Carcinoma a piccole cellule della prostata. Descrizione di un caso.

The case of a 73-year-old man with metastatic small cell carcinoma (SCC) of the prostate is described. Seric neuron-specific enolase (NSE) was enhanced (75.4 ng/mL), while the prostate-specific antigen (PSA) was in the normal range. Therapy with etoposide and carboplatin induced a temporary partial remission, with fairly good quality of life and decrease of the NSE levels (down to 15.0 ng/mL). The patient died approximately 12 months after the initial diagnosis. The case confirms that prostatic SCC (a rare and very aggressive neoplasm) is usually diagnosed in an advanced stage. Treatment is problematic, however chemotherapy may prolong survival allowing, at least temporarly, an acceptable life quality. NSE measurement is useful to differentiate SCC from the more common adenocarcinoma (typically associated with elevated PSA values) and for follow-up.

A re-appraisal of the nature of the atropine-resistant contraction to electrical field stimulation in the human isolated detrusor muscle.

We investigated whether in human isolated detrusor strips the atropine-resistant contractile response to electrical field stimulation was mediated by ATP (or a related purine), as previously shown in the urinary bladder of other mammalian species. Electrical stimulation (1-50 Hz for 5 s at 1 min intervals, 0.1 ms pulse width, 60 V) elicited reproducible, frequency-dependent twitch contractions, which were markedly reduced by atropine (10 microM). Tetrodotoxin (TTX: 1 microM) inhibited contractile responses to a similar degree. When applied together, atropine and TTX caused an inhibition which was superimposable to that caused by either drug alone. The TTX-resistant contractions were totally unaffected by omega-conotoxin GVIA (omega-CTX: 0.1 microM). The atropine-resistant contractions were unaffected by the P2-purinoceptor antagonists suramin (300 microM) and PPADS (30 microM), at concentrations which virtually suppressed the contractile response induced by applied ATP (10 microM(-1) mM). As previously described, antagonism of the ATP-induced contractions by suramin (30, 100, 300 microM) and PPADS (3, 10, 30 microM) was insurmountable, with apparent 'pA2' values (calculated at the lowest antagonist concentrations) of 4.9 and 5.2, respectively. It is concluded that, under our experimental conditions, the non-cholinergic (atropine-resistant) component of the excitatory transmission in the human detrusor is not mediated by neural release of ATP, in spite of the presence of excitatory P2-purinoceptors on the effector cells. The TTX- and omega-CTX-resistant, non-cholinergic component might be related to the release of unknown transmitter(s) through a mechanism independent of both Na+- and N-type Ca2+-channels. More likely, the atropine-resistant component may reflect direct smooth muscle excitation since the human detrusor has a very short chronaxie (Sibley 1984).

[Possible etiologic role of occupational exposure to arsenic anhydride in a case of bladder carcinoma]. / Possible ruolo eziologico dell'esposizione professionale ad anidride arseniosa in un caso di carcinoma vescicale.

It has long been known that occupational or environmental exposure to arsenic (As) may cause skin and lung cancer. Moreover, several epidemiological studies on populations exposed to inorganic As by ingestion indicate an increased risk for cancer at other sites and, particularly, for bladder cancer. We describe the case of a petrol chemical worker, who died of metastasized bladder cancer at the age of 52, after being employed for over 30 years in a hydrogen production unit. Analysis of the technological cycle and biological monitoring data revealed an excessive, prolonged exposure to arsenic trioxide (As2O3) vapours and fumes; a solution of this compound was utilized to absorb the CO2 produced by oxidation of the synthesis gas. Careful anamnesis indicated a prolonged contact between the carcinogen and the bladder mucosa, due to the presence of severe urethral stenosis with chronic urinary obstruction. It also appears likely that synergism between As exposure and smoking (5-10 cigarettes per day until 46 years) occurred. This case suggests the opportunity to extend to the occupational setting future epidemiological research on the relationship between inorganic As exposure and bladder cancer.

5-Hydroxytryptamine receptors that facilitate excitatory neuromuscular transmission in the guinea-pig isolated detrusor muscle.

1. In isolated detrusor strips from the guinea-pig urinary bladder, contractile responses to electrical field stimulation were mostly mediated by neurally released acetylcholine (ACh) and adenosine 5'-triphosphate (ATP). 2. 5-Hydroxytryptamine (5-HT) produced a concentration-dependent increase in the amplitude of stimulated detrusor strip contractions. The 5-HT concentration-response curve showed a biphasic profile: the high potency phase was obtained at sub-micromolar concentrations (10-300 nM), while the low potency phase in the range 1-30 microM. The maximum response of the first phase was 30% of the total 5-HT response. 3. Like 5-HT, the 5-HT3 receptor agonist, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT: 0.3-100 microM), the 5-HT2 receptor agonist, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI: 30 nM-3 microM) and the 5-HT4 receptor agonist, 5-methoxytryptamine (5-MeOT: 0.1-30 microM) potentiated, though with lower potency, detrusor contractions. The resulting concentration-response curves were monophasic in nature. 2-Methyl-5-HT had a maximum effect comparable to that of 5-HT. By contrast, the maximal effects of DOI and 5-MeOT were only 20% and 30% of that elicited by 30 microM 5-HT, respectively. 4. The 5-HT3 receptor antagonist, granisetron (0.3 microM) had no effect on the high potency phase, but caused a rightward parallel shift of the low potency phase of the 5-HT curve (pKB = 7.3). Granisetron(0.3 microM) antagonized with comparable affinity (pKB = 7.1) 5-HT-induced responses after pharmacological isolation of 5-HT3 receptors with the 5-HT1/5-HT2 receptor antagonist, methiothepin (0.3 microM) and the 5-HT4 receptor antagonist, GR 125487 (30 nM). Granisetron (0.1, 0.3 and 1 microM) competitively antagonized the potentiating effect of 2-methyl-5-HT with an estimated pA2 of 7.3.5. Methiothepin (0.3 microM) and the 5-HT2A receptor antagonist, ketanserin (0.3 microM) produced a slight inhibition of the first phase of the 5-HT curve. In the presence of ketanserin, an equimolar concentration of methiothepin was ineffective in further reducing the effect of 5-HT. Similarly, the 5-HT4 receptor antagonist, GR 125487 (30 nM) slightly inhibited the first phase of the 5-HT curve. Conversely, this phase was suppressed when detrusor strips were coincubated with ketanserin (or methiothepin) and GR125487.6. In a separate set of experiments, the interactions of 5-HT with either the purinergic or cholinergic components of excitatory neuromuscular transmission were investigated. In the presence of hyoscine(1 microM), 5-HT was mostly effective at sub-micromolar concentrations, while in the presence of the P2-purinoceptor antagonist, suramin (300 microM), 5-HT-induced potentiation was mainly obtained with micromolar concentrations.7. Thus, in electrically stimulated detrusor strips from guinea-pig, 5-HT potentiated excitatory neuromuscular transmission by activating at least three separate neural 5-HT receptors. These include the 5-HT2A and 5-HT4 receptors, which mediate the 5-HT high potency phase mainly by activation of purinergic transmission. On the other hand, the potentiating effect caused by micromolar concentrations of 5-HT mostly involves cholinergic transmission and is mediated by the 5-HT3 receptors.

Therapeutic potential of drugs with mixed 5-HT4 agonist/5-HT3 antagonist action in the control of emesis.

Drugs interacting with serotonin (5-hydroxytryptamine, 5-HT) receptors are of value in the treatment of several gastrointestinal disturbances. Selective 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) are widely utilized to control emesis induced by chemotherapy and radiation, while agonists at 5-HT4 receptors (cisapride, renzapride, BIMU compounds) are endowed with gastrointestinal prokinetic action. Here we overview the therapeutic potential of drugs with potent mixed 5-HT4 agonist/5-HT3 antagonist properties (i.e. BIMU 1) in the management of anticancer therapy-induced emesis and of intestinal adynamic post-operative conditions associated with vomiting. In the former situation, the agonism at 5-HT4 receptors is expected to be of benefit via two possible mechanism: (i) inhibition of 5-HT release from enterochromaffin cells; (ii) restoration of anally driven peristaltic waves in the upper gastrointestinal tract. Moreover, 5-HT4 receptor-induced prokinetic activity may counteract colonic constipation, an unwanted effect which occurs in a number of patients treated with pure 5-HT3 receptor antagonists. Additionally, the above mentioned drugs might be of value in post-operative conditions associated with intestinal adynamia and emesis sensitive to 5-HT3 receptor blockade.

The interaction of antidepressant drugs with central and peripheral (enteric) 5-HT3 and 5-HT4 receptors.

1. A combined study of receptor binding in central neuronal cell membranes and functional responses in isolated segments of guinea-pig small intestine allowed characterization of the interaction of four antidepressant drugs with central and peripheral 5-HT3 and 5-HT4 receptors. 2. Clomipramine, paroxetine and fluoxetine inhibited [3H]-DAU 6215 binding to 5-HT3 recognition sites in NG 108-15 cells with IC50 values in the range 1.3-4 microM. Litoxetine had an IC50 of 0.3 microM. The specific binding of [3H]-GR 113808 to 5-HT4 recognition sites in pig striatal membranes was inhibited by all four antidepressants with negligible potency (IC50 values > or = 20 microM). 3. In whole ileal segments, concentration-response curves to 5-HT were biphasic, with the high- and low-potency phases involving 5-HT4 and 5-HT3 receptors, respectively. Curves to 2-methyl-5-hydroxytryptamine (2-methyl-5-HT: a 5-HT3 receptor agonist) and 5-methoxytryptamine (5-MeOT: a 5-HT4 receptor agonist) were monophasic. All antidepressants were used at concentrations lacking anticholinoceptor properties, as demonstrated in both electrically stimulated longitudinal muscle-myenteric plexus preparations (LMMPs) and in unstimulated LMMPs following addition of acetylcholine (100 nM). 4. Fluoxetine (0.1-1 microM) and litoxetine (0.3-3 microM) antagonized both the high- and low-potency phases of the 5-HT curve. Schild analysis for the low-potency phase yielded pA2 estimates of 6.6 +/- 0.3 (Schild slope of 1.1) and of 6.6 +/- 0.1 (Schild slope of 1.1), respectively. At higher concentrations (3 microM), fluoxetine markedly inhibited the 5-HT response maximum. Clomipramine (10-300 nM) inhibited, by a mechanism independent of concentration, both phases of the 5-HT curve with a reduction of the maximum response. Paroxetine (1 microM) was ineffective on the high-potency phase, but caused a rightward shift of the low-potency phase (pKB: 6.1 +/- 0.01). 5. Responses to 2-methyl-5-HT were inhibited by 1 microM fluoxetine (pKB: 5.4 +/- 0.02). Like clomipramine(30 and 100 nM), litoxetine (1 and 3 microM) produced rightward displacements of 2-methyl-5-HT-induced contractions, which were virtually independent of antidepressant concentration (pKB values: 6.0 +/- 0.02 and 5.5 +/- 0.01, respectively). At higher concentrations, fluoxetine (3 microM) and clomipramine (300 nM)markedly reduced the 2-methyl-5-HT response maximum. Paroxetine (1 micro M) was ineffective.6. Responses to 5-MeOT were shifted to the right by fluoxetine (0.1-1 micro M) and litoxetine (1 and 3 microM)in a concentration-dependent manner. At higher concentrations, fluoxetine (3 microM) markedly reduced the 5-MeOT response maximum, an effect also observed with 100 and 300 nM clomipramine. Paroxetine(1 microM) was ineffective.7. In unstimulated LMMPs, the excitatory effects evoked by 5-HT, 2-methyl-5-HT and 5-MeOT and the antagonism produced by 300 nM clomipramine were comparable to those obtained in whole ileal segments. This suggests that 5-HT contained in the mucosa of whole preparations does not interfere with agonist-induced contractile responses and with the inhibitory effect of antidepressant drugs.8. In conclusion, our results show that clomipramine, fluoxetine, paroxetine and litoxetine possess low to moderate potency/affinity at both central and peripheral (enteric) 5-HT3 receptors. In contrast, all four antidepressants are virtually ineffective at central 5-HT4 receptors. Inhibition of 5-HT4 receptor mediated ileal contractions by fluoxetine, litoxetine and clomipramine may result from allostericant agonism or, more likely, from post-receptor blockade of second messenger generation. The interaction of antidepressants with central and peripheral 5-HT3 and 5-HT4 receptors may be relevant for both potential therapeutic action and adverse effects at gastrointestinal level.

Nutrition and alcohol neurotoxicity.

Neurological complications of alcoholism such as Wernicke-Korsakoff syndrome and polyneuropathy often originate from interactive factors involving direct nervous system toxicity of ethanol and nutrient deficiencies associated to heavy drinking. Not all patients are equally susceptible to these disorders and a genetic predisposition to thiamine deficiency has been described in subjects with Wernicke's encephalopathy. At moderate alcohol dosages, nutrient abnormalities may be marginal, inducing no obvious manifestations until other neurotoxic agents are absorbed. Examples are presented illustrating the interaction of ethanol and styrene on brain glutathione metabolism in rats, and cases of methanol poisoning in alcoholics. In these patients, ethanol-induced folate deficiency can potentiate visual toxicity of methanol due to impairment of the folate-dependent pathway involved in formate detoxication. The notion that nutritional deficiencies and ethanol toxicity may act synergistically in the nervous system outlines the importance of adequate nutritional strategies in the treatment of alcoholism and also indicates that methodological flaws may result during experimental studies from failure to control for nutritional variables.

Interaction of the neurotoxic pesticides ivermectin and lindane with the enteric GABAA receptor-ionophore complex in the guinea-pig.

In isolated segments of guinea-pig small intestine, gamma-aminobutyric acid (GABA) (3-300 microM), the GABAA receptor agonist 3-aminopropane sulphonic acid (3-APS) (3-300 microM) and ivermectin (1-300 microM) caused concentration-dependent nerve-mediated cholinergic contractions sensitive to tetrodotoxin (1 microM) and hyoscine (1 microM). The EC50 values were 30.2 +/- 4.3, 24.6 +/- 3.1 and 4.8 +/- 0.6 microM, respectively. Picrotoxinin (10 microM), an allosteric blocker of the Cl- channel associated with GABAA receptors, non-competitively antagonized the contractile response caused by each agonist. Like picrotoxinin, lindane (10, 30 microM) caused a dose-related shift to the right of the concentration-response curve to GABA, 3-APS and ivermectin with depression of the maximum response. SR 95531 (3 microM), a competitive antagonist of GABAA receptors, caused a parallel dextral shift of the concentration-response curve to ivermectin with an apparent single point pA2 value of 6.5. Our results suggest that ivermectin and lindane, two neurotoxic pesticides interfering with central GABAErgic transmission, exert agonist and non-competitive antagonist properties at the enteric GABAA receptor-ionophore complex. This peripheral complex can thus be considered as an additional target for the action of both these compounds.

[Indoor pollution: a report of 2 clinical cases of occult carbon monoxide poisoning]. / Inquinamento indoor: presentazione di due casi clinici di ossicarbonismo occulto.

A large part of the general population is potentially exposed to excessive concentrations of carbon monoxide (CO), both in the domestic and work environment. Beside acute, often fatal poisoning, the possibility of occult intoxication should be considered; this condition can affect people who are often unaware of the existence of a toxic exposure in their homes or work places. We describe two non-smoking patients, husband and wife, 53 and 57 years old, respectively, who suffered cephalea, nausea and neurobehavioural disturbances during a period of approximately one year; these symptoms were reported to improve or disappear on several occasions during the patients' absence from home. Careful anamnesis suggested a protracted exposure to nonlethal concentrations of CO contaminating the patients' bed-chamber from the misfunctioning flue of the heating system. It was not possible to measure carboxyhaemoglobinemia until approximately 24 hours since the last presumptive exposure. The levels found were therefore relatively low (4-5%), yet higher than the reference values for normal non-smoking subjects. Carboxyhaemoglobin concentrations almost returned into the normal range during the period of hospitalization. These two cases exemplify how low level CO exposure may cause aspecific pathological manifestations that are often misdiagnosed or overlooked.

Interaction of aluminum ions with phosphoinositide metabolism in rat cerebral cortical membranes.

Aluminum (Al) is believed to exert a primary role in the neurotoxicity associated with dialysis encephalopathy and has been suggested to be involved in a number of other neurological disorders, including Alzheimer's disease. Al, complexed with fluoride to form fluoroaluminate (AlF4-), can activate the GTP-binding (G) proteins of the adenylate cyclase and retinal cyclic GMP phosphodiesterase systems. Since an involvement of G-proteins with cerebral phosphoinositide (PtdIns) metabolism has also been suggested, in this study we investigated the interaction of the stable GTP analogue GTP(S), Al salts and NaF with this system. In rat cerebral cortical membranes, GTP(S) dose-dependently stimulated [3H]inositol phosphates ([3H]InsPs) accumulation. This effect was potentiated by carbachol and was partially prevented by the GTP-binding antagonist GDP(S), indicating that CNS muscarinic receptor activation is coupled to PtdIns hydrolysis via putative G-protein(s). GTP(S) stimulation was also inhibited by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, which is known to exert a negative feedback control on agonist-stimulated PtdIns metabolism. Both Al salts and NaF mimicked the action of GTP(S) in stimulating PtdIns turnover. Their actions were highly synergistic, suggesting that AlF4- could be the active stimulatory species. However, the stimulatory effects of AlCl3 and/or NaF were not potentiated by carbachol and were not inhibited by GDP(S) and PMA, suggesting that separate sites of action might exist for GTP(S) and AlF4-. In the nervous tissue, activation of PtdIns hydrolysis by Al (probably as AlF4-) may be mediated by activating a regulatory G-protein at a location distinct from the GTP-binding site or by a direct stimulation of phospholipase C.

Trichloroethylene: toxicology and health hazards.

Trichloroethylene (TCE), a synthetic compound widely used in many occupational and non-occupational settings, is one of the leading environmental contaminants. In this paper, current information on sources, human exposure, metabolism, toxicology and health impact of TCE is reviewed. The central nervous system is the major target for TCE toxicity. This compound, however, can also exert toxic effects on other tissues and organs, for example the myocardium, the kidney and the liver. Several rodent bioassays indicate that TCE is a carcinogen for laboratory animals. Human carcinogenicity, however, is still controversial as there are limited epidemiological studies available for assessment and important species differences in metabolism that make extrapolation from animal studies more challenging. Current regulatory standards are discussed in connection with the analysis of technical and medical prevention.